Penetration of ciprofloxacin, norfloxacin and ofloxacin into the aqueous humours of patients by different topical application modes.
OBJECTIVE
A prospective study was undertaken to determine the transcorneal penetration of three topically applied fluoroquinolones into aqueous humour.


METHODS
Two hundred and twenty-four patients undergoing cataract extraction received 0.3% ciprofloxacin, norfloxacin or ofloxacin eye drops by two different administration modes with different frequencies and intervals of application. At the beginning of cataract extraction (0.5-3 h after the last drop), 50-100 microliters aqueous fluid was aspirated from the anterior chamber and immediately stored at -80 degrees C. Antibiotic concentrations were measured using high-performance liquid chromatography.


RESULTS
Generally, topical ofloxacin and ciprofloxacin yielded aqueous humour levels higher than topical norfloxacin. The highest concentrations of all tested fluoroquinolones were measured after using an application mode, in which one drop was given every 15 min between 0600 hours and 0800 hours, prior to operation. When applied by this mode, ciprofloxacin achieved a mean aqueous level of 0.380 (+/- 0.328) microgram.ml-1 (range 0.033-1.388 micrograms.ml-1), norfloxacin 0.182 (0.118) microgram.ml-1 (range 0.038-0.480 microgram.ml-1) and ofloxacin 0.564 (0.372) microgram.ml-1 (range 0.064-1.455 micrograms.ml-1). These mean concentrations were above the minimum inhibitory concentration (MIC90), concentrations required for inhibition of 90% of pathogen strains in vitro of gram-negative bacteria, such as Proteus mirabilis and Escherichia coli. Therapeutic values above the MIC90 of Staphylococcus epidermidis, the pathogen causing eye infections most frequently, were reached by 67.5% of patients after ofloxacin and by 41% after ciprofloxacin, but never after norfloxacin treatment.


CONCLUSIONS
Of the currently available topical fluoroquinolones, ofloxacin achieved the highest aqueous humour concentration. This fluoroquinolone may be an useful ophthalmic agent for topical antibacterial management, but it does not seem to be prophylactically effective against Streptococcus pneumoniae or Pseudomanas aeruginosa.
von Keyserlingk
J
J
Department of Clinical Pharmacology, Medizinische Fakultät, Universität Rostock, Germany.
Beck
R
R
Fischer
U
U
Hehl
E M
EM
Guthoff
R
R
Drewelow
B
B
D000287:Administration, Topical; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000890:Anti-Infective Agents / Q000493:pharmacokinetics*; D001082:Aqueous Humor / Q000378:metabolism*; D002939:Ciprofloxacin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009643:Norfloxacin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D015242:Ofloxacin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011446:Prospective Studies
D000890:Anti-Infective Agents; D002939:Ciprofloxacin; D015242:Ofloxacin; D009643:Norfloxacin